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临床实践中1型人类免疫缺陷病毒(HIV-1)感染患者对含马拉维若的抗逆转录病毒治疗方案的病毒学和免疫学反应:不同嗜性检测结果及联合治疗的作用

Virological and immunological response to antiretroviral regimens containing maraviroc in HIV type 1-infected patients in clinical practice: role of different tropism testing results and of concomitant treatments.

作者信息

Rossetti Barbara, Bianco Claudia, Bellazzi Lara Ines, Bruzzone Bianca, Colao Grazia, Corsi Paola, Monno Laura, Pagano Gabriella, Paolucci Stefania, Punzi Grazia, Setti Maurizio, Zazzi Maurizio, De Luca Andrea

机构信息

1 Infectious Diseases Clinic, AOU , Senese, Italy .

出版信息

AIDS Res Hum Retroviruses. 2014 Jan;30(1):17-24. doi: 10.1089/AID.2012.0235. Epub 2013 Sep 17.

Abstract

We assessed the immunovirological response to antiretroviral regimens containing maraviroc in HIV-infected viremic patients with viral tropism predicted by different assays. We selected antiretroviral treatment-experienced HIV-1-infected patients initiating regimens containing maraviroc after different phenotypic or genotypic viral tropism assays, with at least one HIV-1 RNA determination during follow-up. Survival analysis was employed to assess the virological response as time to HIV-1 RNA <50 copies/ml and immunological response as time to a CD4 cell count increase of ≥ 100/μl from baseline. Predictors of these outcomes were analyzed by multivariate Cox regression models. In 191 treatments with maraviroc, virological response was achieved in 65.4% and the response was modestly influenced by the baseline viral load and concomitant drug activity but not influenced by the type of tropism assay employed. Immunological response was achieved in 58.1%; independent predictors were baseline HIV-1 RNA (per log10 higher: HR 1.29, 95% CI 1.05-1.60) and concomitant therapy with enfuvirtide (HR 2.05, 0.96-4.39) but not tropism assay results. Of 17 patients with baseline R5-tropic virus and available tropism results while viremic during follow-up on maraviroc, seven (41%) showed a tropism switch to non-R5 virus. A significant proportion of experienced patients treated with regimens containing maraviroc achieved virological response. The tropism test type used was not associated with immunovirological response and concomitant treatment with enfuvirtide increased the chance of immunological response. More than half of virological failures with maraviroc were not accompanied by tropism switch.

摘要

我们评估了在通过不同检测方法预测病毒嗜性的HIV感染病毒血症患者中,对含马拉维若的抗逆转录病毒治疗方案的免疫病毒学反应。我们选择了在经历不同表型或基因型病毒嗜性检测后开始含马拉维若方案治疗的有抗逆转录病毒治疗经验的HIV-1感染患者,随访期间至少进行一次HIV-1 RNA测定。采用生存分析评估病毒学反应,即达到HIV-1 RNA<50拷贝/ml的时间,以及免疫反应,即CD4细胞计数从基线增加≥100/μl的时间。通过多变量Cox回归模型分析这些结果的预测因素。在191次使用马拉维若的治疗中,65.4%实现了病毒学反应,该反应受基线病毒载量和伴随药物活性的适度影响,但不受所用嗜性检测类型的影响。58.1%实现了免疫反应;独立预测因素为基线HIV-1 RNA(每高log10:HR 1.29,95%CI 1.05-1.60)和与恩夫韦肽联合治疗(HR 2.05,0.96-4.39),但不受嗜性检测结果影响。在17例基线为R5嗜性病毒且在接受马拉维若随访期间病毒血症时有可用嗜性结果的患者中,7例(41%)显示嗜性转变为非R5病毒。接受含马拉维若方案治疗的相当一部分有经验的患者实现了病毒学反应。所用嗜性检测类型与免疫病毒学反应无关,与恩夫韦肽联合治疗增加了免疫反应的机会。超过一半的马拉维若病毒学失败未伴有嗜性转变。

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